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Dolly made front pages around the world because of her startling pedigree: Dolly, ... not from embryonic cells but from the mammary gland of a mature, 6-year old ewe. ...
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1. Animal pharming: transgenic and cloned animals
The process of using transgenic or cloned animals to produce human drugs Dolly made front pages around the world because of her startling pedigree: Dolly, unlike any other mammal that has ever lived, is an identical copy of another adult and has no father. She is a clone, the creation of a group of veterinary researchers. That work, performed by Ian Wilmut and his colleagues at the Roslin Institute in Edinburgh, Scotland, has provided an important new research tool and has shattered a belief widespread among biologists that cells from adult mammals cannot be persuaded to regenerate a whole animal. Although the Scottish researchers have made clear that they would consider it unethical to adapt their technique to clone humans (Wilmut is a member of a working group on the ethics of genetic engineering), the demonstration has raised the uncomfortable prospect that others might not be so scrupulous. Cloning humans would mean that women could in principle reproduce without any help from men. Scientific American, 1997 Wilmut and his co-workers accomplished their feat by transferring the nuclei from mature somatic sheep cells into unfertilized sheep eggs from which the natural nuclei had been removed by microsurgery. Once the transfer was complete, the recipient eggs contained a complete set of genes, just as they would if they had been fertilized by sperm. The eggs were then cultured for a period before being implanted into sheep that carried them to term, one of which culminated in a successful birth. The resulting lamb was, as expected, an exact genetic copy, or clone, of the sheep that provided the transferred nucleus, not of those that provided the egg. Other researchers have previously cloned animals, including mammals, by transferring nuclei from embryonic cells into such enucleated eggs. The interest in the new work, published in the February 27, 1997, Nature, is that some of the transferred nuclei that gave rise to lambs came not from embryonic cells but from the mammary gland of a mature, 6-year old ewe. Other workers have failed to produce viable offspring when they attempted equivalent experiments. The key to success at the Roslin Institute seems to have been that Wilmut starved the mammary cells for five days before extracting their nuclei. This maneuver "froze" the cells in a quiescent phase of their division cycle and may have made their chromosomes more susceptible to being reprogrammed to initiate the growth of a new organism after the nuclei were transferred into an egg. It required 277 nuclear transfers to produce the single, viable cloned lamb. Wilmut's experiment provides a long-sought confirmation that adult cells do in fact contain workable versions of all the genes necessary to produce an entire organism. On February 14, 2003 Dolly was put to sleep. She was 6 years old, and had been diagnosed with progressive lung disease. Was it an early death, was it because she was a clone? Sheep live 11-12 years Dolly came from a 6 years old ewe The telomerases were shorter She had arthritis on her hind legs Lung disease is common in older sheep She had three healthy lambs before she got sick Conclusions? Animal Pharming: The industrialization of Transgenic Animals Transgenic animals express one or more human genes . The inserted genes, when successful, enables an animal to make the desired pharmaceutical in their milk, urine, blood, sperm or egg, or to grow organs resistant to rejection after transplants. Currently there are more than a dozen different molecules produced by pharm animals and used for therapeutic purposes. These include treatment for cystic fibrosis, hemophilia, osteoporosis, arthritis, malaria, and HIV. Transgenic animals can also produce monoclonal antibodies that are used for the development of vaccines Transgenic animals are costly: 20,000-30,000 for one animal, and low chances of success. If successful, one animal can produce in its life time 200,000-300,000 million worth of drugs. A herd of 600 transgenic cows could supply the worldwide demand of human serum albumin (used in the treatment of burns and traumatic injuries) Traditional methods to produce recombinant proteins -Laboratory cell cultures of transgenic bacteria, yeast, or animal cells Disadvantages: -Cultures require constant monitoring -Expression is more costly, because substantial machinery must be purchased and maintained -Isolating and purifying proteins is more difficult than purifying proteins from an animals milk or bodily fluid. Animal bioreactors are more cost-effective, they have the cellular machinery to produce complex proteins, recombinant proteins come out from milk 99% pure. Any other advantage? Bacteria-vs mammalian cells The first trangenic animal produced was a mouse (1981). A gene was inserted into this mouse that made him susceptible to cancer. In 1985 the first transgenic farm animal was made, a sheep called Tracy. Tracy had a human gene that expressed high levels of human anti-trypsin. The protein , when missing in humans, can lead to a rare form of enphysema. Most recently, the enviro pig has been developed. This pig has a phytase gene placed in its salivary glands to allow better utilization of phosphorus in feedstuff. The enviro pig may prove to be part of the solution to animal waste issues. In Wisconsin 37 cows were cloned in 1999, 17 of them were transgenic. The cost is projected to go down to $5,000 per animal. A human gene responsible for producing a desired protein Is isolated in a laboratory. 2. An animal is given hormonal treatment to produce a large number Of embryos, and the embryos are collected from the oviduct. 3. The human gene is inserted into the fertilized egg via microinjection 4. The transgenic embryo is placed in a surrogate host which gives Birth to the transgenic animal 5. The offspring is tested for the new gene
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